I.Enantioselective total synthetic approaches to manzamine A and dynemicin AI) Synthesis of the tetracyclic core of manzamine A (1) was achieved via Diels-Alder reaction of the dihydropyridinones. Conversion of the two D-A products to the key tricyclic ketone was conducted through a conventional pathway as well as a new pathway developed.2) The highly stereoselective synthesis of the optically active tetracyclic core of Manzamine A was achieved via the Diels-Alder reaction of dihydropyridinone, derived from L-serine, with siloxydienes, followed by sequential new and conventional pathways.3) Preparation of the 1-methoxycarbonyl-3-phenylthio-2-quinolinone from dihydro-2-quinolinone and its Diels-Alder reaction with 2-trimethylsilyloxy- 1, 3-butadiene and 2-TMSO- 1, 3-pentadiene under Lewis acid catalyst was developed. Conversion of the D-A adduct to 9-phenanthridinone ketal will open a new synthetic route to a dynemicin A core structure.4). We found an efficient synthesis of a, beta-unsa
… Moreturated ketones by the reaction of acid chlorides with trialkylaluminum (1/3 mole equiv) in the presence of AlC13 (I mol equiv).II.Both L-threo and D-ervthro-1-phenyl-2-palmitoylamino-3-morpholino- 1-propanol (PPMP) and the decanoyl derivative (PDMP) were synthesized stereselectively from L-serine.III.The crystal structure of Vsr endonuclease was determined by X-ray analysis.IV.The first example of a reagent-controlled enantioselective Pictet-Spengler reaction was achieved. Using diisopinocampheylchloroborane as a chiral Lewis acid catalyst, the Pictet-Spengler reaction of Nb-hydroxytryptamine with aldehydes gave the corresponding 2-hydroxytetrahydro-beta-carbolines in up to 90% ee. The enantioselective Pictet-Spengler reaction catalyzed by chiral binaphthol-derived Brphindted acid-assisted Lewis acids, with up to 91% ee, was also achieved.2. 新規抗マラリア剤の開発を目的とするスフィンゴ脂質の合成III. DNA修復酵素Vsrの合成、およびそのDNA認識機構、解裂機構の解析Vsrタンパクは、5-メチルシトシンの加水分解により生じるG-Tミスマッチを選択的に認識し、backboneの切断を行う分子量18kdaのDNA修復タンパクである。しかし、その3次元構造、ならびに分子レベルでの配列認識およびDNA鎖切断の機構は未知である。本研究においては、タンパクの3次元構造、ならびに分子レベルでの配列認識およびDNA鎖切断の機構の解明を目指し、Vsrタンパクの過剰発現ならびに、結晶化に成功した。さらに基質となるオリゴヌクレトチドのタンパクの存在の有無による構造変化をNMRを用いて検討し、配列記識の機構を解明した。IV. 光学活性アミン類の不斉合成1. 初のエナンチオ選択的Pictet-Spengler反応に成功した。2. イミンのジアステレオ選択的アルキル化反応で中〜高い選択性を見い出した。 Less